Darcy B. Kelley
Columbia
University
Biological Sciences
911 Fairchild Center, M.C. 2432
New York, N.Y. 10027
212-854-5108
E-mail dbk3@columbia.edu
Co-Director, Doctoral Subcommittee in Neurobiology & Behavior
Neurobiology Courses:
Undergraduate : W3005
Graduate : W4005 |
G6002 | G9002
| G9010
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of Neurobiology
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Organisms generally come in two flavors, male and female. We study the
biological origins of the differences between the sexes; in particular, the
physiological, developmental, cellular, molecular and evolutionary mechanisms
that underlie the actions of gonadal steroid
hormones, androgen and estrogen. Sex-specific vocal behaviors of the South
African clawed frog, Xenopus laevis, provide our experimental preparation.
Vocal behaviors are used to signal sexual receptivity and unreceptivity, dominance and territoriality; each sex has a
distinct and behaviorally powerful repertoire of songs. During a recent field
season in
Songs are generated by rapid contractions of intrinsic laryngeal muscles in response to patterned activity in the laryngeal nerves. The isolated larynx can produce actual vocalizations, and we can record from the laryngeal nerve of singing frogs. These experimentally favorable preparations permit identification of male- and female-specific electrophysiological and muscular characteristics which underlie the different vocal repertoires of the sexes. We utilize a larynx/brain preparation to examine sexually differentiated motor programs using intracellular recording patch clamp and tracing techniques. Sex differences in the larynx included synaptic efficacy - weak synapses in males versus strong synapses in females- and in muscle fiber type - rapidly contracting fibers in males and slowly contracting fibers in females. Estrogen controls the efficacy of the laryngeal synapse. We are examining synaptic vesicle associated proteins to explore the mechanisms by which estrogen increases synaptic strength. Muscle contraction rate is tied to expression of an androgen-regulated, embryonic-like myosin. Prolactin secretion opens the sensitive period for androgen regulation of this myosin; the molecular basis of this action is not yet known.
Many sexually differentiated characteristics are due to sex differences in hormone secretion during development and adulthood. Androgen controls sexually differentiated vocal development by regulating cell numbers and types. We are exploring the trophic actions of androgen by examining how this hormone stimulates cell proliferation and prevents cell death. We are using a related frog species, Xenopus tropicalis, with a more tractable genotype and generation time, to identify the downstream targets of androgen action that lead to the masculine behavioral phenotype.
Which tissues develop in a sexually differentiated form and which do not is determined by the expression of specific steroid receptors, which genes are regulated by those hormones and how alterations in gene expression affect cell/cell interactions. The androgen receptor may play two distinct roles during development: an early role in the formation of the nervous system and the axial skeleton and a later role in sexual differentiation. We are using a relatively new experimental approach, transgenic Xenopus, to explore these roles for the androgen receptor.
What are the evolutionary origins of steroid receptors? A comparison of all
available androgen receptor and other steroid receptor sequences reveals a
group of amino acids that "diagnose" the clade
of ARs -- residues that are strictly conserved among
the ARs but not shared with other receptors. These
amino acids, clustered in a few regions of the protein, must confer upon the
androgen receptor its unique functions, including recognition of specific DNA
response elements and affinity for androgens rather than other steroid
hormones. The four domains of the AR display markedly different rates of
evolutionary divergence; possible functions of these different androgen
receptor domains in early development and later sexual differentiation are
under investigation.
Current Lab Members | Current & Former Labbies E-mail Addresses
Representative Publications
Vignal, C., Kelley, D. B 2007. Significance of temporal and spectral acoustic cues for sexual recognition in Xenopus laevis. Proc. R. Soc, 274, 479-488. [pdf]
Kelley, D.B. 2004. Vocal communication in frogs. Current Opinion in Neurobiology, 14:751-757. [pdf]
Tobias, M.L., Barnard, C., O'Hagan, R., Horng, S.,
Yamaguchi, A. and Kelley, D.B. 2002. Hormonal mechanisms of acoustic communication. In Acoustic
Communication, A. Megala-Simmons, A. Popper and R.
Fay, Eds. Springer Verlag,
Kelley, D.B. 2002. Hormonal
regulation of motor output in amphibians; Xenopus
laevis vocalizations as a model system. In
Hormones,Brain and Behavior, D. Pfaff, A. Arnold, A. Etgen, S. Fahrbach and R. Rubin (Eds), Academic Press,
in press. [pdf]
Kelley, D. B. and Tindall,
D.W. 2002. Model systems for the study of androgen regulated gene
expression in the central nervous system, In Hormones, Brain and Behavior, D.
Pfaff, A. Arnold, A. Etgen, S. Fahrbach
and R. Rubin (Eds), Academic Press, in press. [pdf]
Breedlove, M,
Wu, K.H., Tobias, M.L. and Kelley, D.B. 2001. Estrogen and laryngeal synaptic strength in Xenopus
laevis; opposite effects of acute and chronic
exposures. Neuroendocrinology 486: 1 - 11. [pdf]
Kelley, D.B. 2001. Is song special? Neuron 31:508-10. [pdf]
Edwards, C. and Kelley, D.B. 2001. Auditory and lateral line inputs to the midbrain of an aquatic anuran: neuroanatomical studies in Xenopus laevis. J. Comp. Neurol., 438, 148 - 162. [pdf]
Kelley, D.B., Tobias, M.L. and Horng, S. 2001. Producing and perceiving frogs songs; dissecting the neural bases for vocal behaviors in Xenopus laevis. In Anuran Communication, M. Ryan (Ed), Smithsonian Institution Press, pp. 156 - 166. [pdf]
Yamaguchi A, Kaczmarek LK, Kelley, D.B.
2000. Intrinsic membrane properties of laryngeal motoneurons
that control sexually differentiated vocal behavior in African clawed frogs, Xenopus laevis. Biol Bull 2000 199:175-6 [pdf]
Yamaguchi, A. and Kelley, D.B. 2000. Generating
sexually differentiated vocal patterns: laryngeal nerve and EMG recordings from
vocalizing male and female African clawed frogs (Xenopus
laevis). J. Neurosci.,
20: 1559 - 1567. [pdf]
Edwards, C.J., Yamamoto, K., Kikuyama, S. and Kelley, D.B. 1999. Prolactin opens the sensitive period for androgen regulation of a larynx-specific myosin heavy chain gene. J. Neurobiol., 41, 453 - 451. [pdf]
Kay, J.N, Hannigan, P. and Kelley, D.B. 1999. Trophic effects of androgen: Development and hormonal regulation of neuron number in a sexually dimorphic vocal motor nucleus. J. Neurobiol., 40, 375 - 385. [pdf]
Kelley, D.B. and Tobias, M.L. 1999 The vocal
repertoire of Xenopus laevis.
In The Design of Animal Communication, M. Hauser and M. Konishi, Eds., MIT Press,
Tobias, M., Tomasson, J. and Kelley, D.B. 1998. Attaining and maintaining strong vocal synapses in female Xenopus laevis, J. Neurobiol., 37, 441 -448. [pdf]
Tobias, M.L.,Viswanathan,
S. and Kelley, D.B. 1998. Rapping, a female receptive call, initiates
male/female duets in the South African clawed frog, Proc. Natl. Acad. Sci., 95:1870 - 1875. [pdf] [ABC
News Article]
Ruel, T.,
Kelley, D. and Tobias, M. 1998. Facilitation at
the sexually differentiated laryngeal synapse of Xenopus
laevis, J. Comp. Physiol.,
1 - 42.
Abstract [pdf]
Evans, B.J., Morales, J.C., Picker, M.D., Melnick,
D.J., and Kelley, D.B. 1998. Absence of extensive introgression between Xenopus gilli and Xenopus laevis laevis (Anura: Pipidae) in Southwestern Cape Province,
Perez,J. and Kelley, D.B. 1997. Androgen mitigates axotomy-induced decreases in calbindin expression in motoneurons, J. Neurosci., 17: 7396-7403. Abstract [pdf]
Kelley, D. 1997 Generating sexually differentiated songs. Current Opinion in Neurobiology, 7, 839 - 843. Abstract [pdf]
Evans, B., Morales, J., Picker, M., Kelley, D.B. and Melnick, D. (1996). Comparative molecular phylogeography of two Xenopus species, X. gilli and X. laevis, in the South-western Cape Province, South Africa, Molecular Ecology, 6:333-343. Abstract [pdf]
Perez, J. and Kelley, D. (1996). Trophic effects of androgen: receptor expression and the survival of laryngeal motor neurons after axotomy. J. Neuroscience, 16:6625-6633. Abstract [pdf]
Cohen, M. and Kelley, D. (1996). Androgen induced proliferation in the developing larynx of Xenopus laevis is regulated by thyroid hormone. Dev. Biol. 178:113-123. Abstract [pdf]
Perez, J., Cohen, M.A. and Kelley, D.B. (1996). Androgen receptor mRNA expression in Xenopus laevis; sexual dimorphism and regulation in the laryngeal motor nucleus. J. Neurobiol. 30:556-568. Abstract [pdf]
Robertson, J. and Kelley, D. (1996). Thyroid hormone controls the onset of androgen sensitivity in the developing larynx of Xenopus laevis. Dev. Biol. 176:108-123. Abstract [pdf]
Kelley, D. (1996). Sexual
differentiation in Xenopus laevis. The Biology of Xenopus. R. Tinsely
and H. Kobel (Eds.),
Catz, D., Fischer, L. and Kelley, D. (1995) Androgen regulation of a laryngeal-specific myosin heavy chain isoform whose expression is sexually differentiated. Developmental Biology 171:448-457Abstract [pdf]
Tobias, M., Kelley, D. and Ellisman, M. (1995) A sex difference in synaptic efficacy at the laryngeal neuromuscular junction of Xenopus laevis. J. Neurosci, 15:1660-1668.Abstract [pdf]
Fischer, L.M., Catz, D.S. & Kelley, D.B (1995) Androgen-Directed Development of the Xenopus Laevis Larynx: Control of Androgen Receptor Expression and Tissue Differentiation. Dev. Biol.; 170:115-126 [pdf]
Kang, L., Marin, M. and Kelley , D. 1995. Androgen biosynthesis and secretion in developing Xenopus laevis, Gen. Comp. Endocrinol., 100, 293 - 307. [pdf]
Tobias, M. and Kelley, D.B. 1995. Sexual differentiation and endocrine regulation of the laryngeal synapse in Xenopus laevis, J. Neurobiol., 28, 515 - 526. [pdf]
Robertson JC, Watson JT, Kelley DB Androgen directs sexual differentiation of laryngeal innervation in developing Xenopus laevis. J Neurobiol 1994 Dec;25(12):1625-1636 Abstract [pdf]
Fischer, L., Catz, D. & Kelley, D.
(1993) An androgen receptor mRNA isoform
associated with hormone-induced cell proliferation. Proc Natl
Acad Sci
Tobias, M.L., Marin, M.L. & Kelley, D.B. (1993) The roles of sex, innervation, and androgen in laryngeal muscle of Xenopus laevis. J.Neurosci 13:324-333. Abstract [pdf]
Watson JT, Robertson J, Sachdev U, Kelley DB Laryngeal muscle and motor neuron plasticity in Xenopus laevis: testicular masculinization of a developing neuromuscular system. J Neurobiol 1993 Dec;24(12):1615-1625. Abstract [pdf]
Catz, D.S., Fischer, L.M., Moschella, M.C., Tobias, M.L. & Kelley, D.B. (1992) Sexually dimorphic expression of a laryngeal-specific androgen-regulated myosin heavy chain gene during Xenopus laevis development. Dev. Biol. 154:366-76. Abstract [pdf]
Watson JT, Kelley DB Testicular masculinization of vocal behavior in juvenile female Xenopus laevis reveals sensitive periods for song duration, rate, and frequency spectra. J Comp Physiol [A] 1992 Oct;171(3):343-350 Abstract [pdf]
Fischer, L.M. & Kelley, D.B. (1991) Androgen receptor expression and sexual differentiation of effectors for courtship song in Xenopus Laevis. The Neurosciences; Vol. 3:469-480 [pdf]
Tobias, M.L., Marin, M.L. & Kelley, D.B. (1991) Temporal constraints on androgen directed laryngeal masculinization in Xenopus laevis. Dev. Biol. 147:260-70. Abstract [pdf]
Tobias, M.L., Marin, M.L. & Kelley, D.B. (1991) Development of functional sex differences in the larynx of Xenopus laevis. Dev. Biol. 147:251-9. Abstract [pdf]
Marin, M.L., Tobias, M.L. & Kelley, D.B. (1990) Hormone-sensitive stages in the sexual differentiation of laryngeal muscle fiber number in Xenopus laevis. Development 110:703-711. Abstract [pdf]
He, W.W., Fischer, L.M., Sun, S., Bilhartz, D.L., Zhu, X.P., Young, C.Y., Kelley, D.B. & Tindall, D.J. (1990) Molecular cloning of androgen receptors from divergent species with a polymerase chain reaction technique: complete cDNA sequence of the mouse androgen receptor and isolation of androgen receptor cDNA probes from dog, guinea pig and clawed frog. Biochem. Biophys. Res. Commun. 171:697-704. Abstract [pdf]
Kelley DB, Dennison J The vocal motor neurons of Xenopus laevis: development of sex differences in axon number. J Neurobiol 1990 Sep;21(6):869-882 Abstract [pdf]
Kelley DB, Hayes M Amphibian experimental systems: developmental neurobiology and behavioral endocrinology in the clawed frog, Xenopus laevis. J Exp Zool Suppl 1990;4:148-149 Abstract
Tobias, M.L. & Kelley, D.B. (1988) Electrophysiology and dye-coupling are sexually dimorphic characteristics of individual laryngeal muscle fibers in Xenopus laevis. J Neurosci 8:2422-9. Abstract [pdf]
Kelley DB, Fenstemaker S, Hannigan P, Shih S. Sex differences in the motor nucleus of cranial nerve IX-X in Xenopus laevis: a quantitative Golgi study. J Neurobiol 1988 Jul;19(5):413-429 Abstract [pdf]
Kelley DB. Sexually dimorphic behaviors. Annu Rev Neurosci 1988;11:225-251 Abstract [pdf]
Segil, N., Silverman, L. & Kelley, D.B. (1987) Androgen-binding levels in a sexually dimorphic muscle of Xenopus laevis. Gen Comp Endocrinol 66:95-101.Abstract [pdf]
Gorlick, D.L. & Kelley, D.B. (1987) Neurogenesis in the vocalization pathway of Xenopus laevis. J Comp Neurol 257:614-627. Abstract [pdf]
Tobias, M.L. & Kelley, D.B. (1987) Vocalizations by a sexually dimorphic isolated larynx: peripheral constraints on behavioral expression. J Neurosci 7:3191-7. Abstract [pdf]
Sassoon, D.A., Gray, G.E. & Kelley, D.B. (1987) Androgen regulation of muscle fiber type in the sexually dimorphic larynx of Xenopus laevis. J Neurosci 7:3198-206. Abstract [pdf]
Kelley DB, Bockman RS, Weintraub A Prostaglandin regulation of reproductive behaviors in female Xenopus laevis: sources and target sites. Adv Prostaglandin Thromboxane Leukot Res 1987;17B:1133-1135 Abstract
Sassoon, D., Segil, N. & Kelley, D.B. (1986) Androgen-induced myogenesis and chondrogenesis in the larynx of Xenopus laevis. Dev Biol 113:135-140. Abstract [pdf]
Dworkin-Rastl, E., Kelley, D.B. & Dworkin, M.B. (1986) Localization of specific mRNA sequences in Xenopus laevis embryos by in situ hybridization. J Embryol Exp Morphol 91:153-68. Abstract [pdf]
Sassoon, D. & Kelley, D.B. (1986) The sexually dimorphic larynx of Xenopus laevis: development and androgen regulation. Am J Anat 177:457-72. Abstract [pdf]
Bass AH, Segil N, Kelley DB. Androgen binding in the brain and electric organ of a mormyrid fish. Comp Physiol [A] 1986 Oct;159(4):535-544 Abstract [pdf]
Gorlick DL, Kelley DB. The ontogeny of androgen receptors in the CNS of Xenopus laevis frogs. Brain Res 1986 May;391(2):193-200 Abstract [pdf]
Kelley DB Neuroeffectors for vocalization in Xenopus laevis: hormonal regulation of sexual dimorphism. J Neurobiol 1986 May;17(3):231-248 Abstract [pdf]
Hannigan P, Kelley DB. Androgen-induced alterations in vocalizations of female Xenopus laevis: modifiability and constraints. J Comp Physiol [A] 1986 Apr;158(4):517-527 Abstract [pdf]
Simpson HB, Tobias ML, Kelley DB. Origin and identification of fibers in the cranial nerve IX-X complex of Xenopus laevis: Lucifer Yellow backfills in vitro. J Comp Neurol. 1986 Feb 22; 244(4): 430-444. Abstract [pdf]
Dworkin-Rastl E, Kelley DB,
Roy EJ, Wilson MA, Kelley DB Estrogen-induced progestin receptors in the brain and pituitary of the South African clawed frog, Xenopus laevis. Neuroendocrinology. 1986; 42(1): 51-56. Abstract [pdf]
Weintraub AS, Kelley DB, Bockman RS Prostaglandin E2 induces receptive behaviors in female Xenopus laevis. Abstract [pdf]
Wetzel DM, Haerter UL, Kelley DB. A proposed
neural pathway for vocalization in South African clawed frogs, Xenopus laevis. J Comp Physiol [A]. 1985 Dec;
157(6): 749-761. Abstract
[pdf]
Wetzel DM, Kelley DB Androgen and gonadotropin effects on male mate calls in South African clawed frogs, Xenopus laevis. Horm Behav. 1983 Dec; 17(4): 388-404. Abstract [pdf]
Paton JA, Kelley DB, Sejnowski TJ, Yodlowski ML Mapping the auditory central nervous system of Xenopus laevis with 2-deoxyglucose autoradiography. Brain Res. 1982 Oct 7; 249(1): 15-22. Abstract [pdf]
Nottebohm F, Kelley DB, Paton JA Connections of vocal control nuclei in the canary telencephalon. J Comp Neurol. 1982 Jun 1; 207(4): 344-357. Abstract [pdf]
Kelley DB. Female sex behaviors in the South African clawed frog, Xenopus laevis: gonadotropin-releasing, gonadotropic, and steroid hormones. Horm Behav. 1982 Jun; 16(2): 158-174. No abstract available. [pdf]
Kelley DB. Locations of androgen-concentrating cells in the brain of Xenopus laevis: autoradiography with 3H-dihydrotestosterone. J Comp Neurol. 1981 Jun 20; 199(2): 221-231. Abstract
Erulkar, S.D., Kelley, D.B., Jurman, M.E., Zelman, F.P., Schneider, G.T. & Krieger,
N.R. (1981) Modulation of the neural control of the clasp reflex in male Xenopus laevis by
androgens: a multidisciplinary study. Proc Natl Acad Sci
Kelley, D.B. (1980) Auditory and vocal nuclei in the frog brain concentrate sex hormones. Science 207:553-555. Abstract [pdf]
Sejnowski TJ,
Wetzel DM, Kelley DB, Campbell BA Central control of ultrasonic vocalizations in neonatal rats: I. Brain stem motor nuclei. J Comp Physiol Psychol. 1980 Aug; 94(4): 596-605. Abstract
Kelley DB, Nottebohm F Projections of a telencephalic auditory nucleus-field L-in the canary. J Comp Neurol. 1979 Feb 1; 183(3): 455-469. Abstract
Kelley DB, Lieberburg I, McEwen BS, Pfaff DW Autoradiographic and biochemical studies of steroid hormone-concentrating cells in the brain of Rana pipiens. Brain Res. 1978 Jan 27; 140(2): 287-305. Abstract [pdf]
Kelley DB, Pfaff DW Hormone effects on male sex behavior in adult South African clawed frogs, Xenopus laevis. Horm Behav. 1976 Jun; 7(2): 159-182. Abstract
Morrell JI, Kelley DB, Pfaff DW Autoradiographic localization of hormone-concentrating cells in the brain of an amphibian, Xenopus laevis. II. Estradiol. J Comp Neurol. 1975 Nov 1; 164(1): 63-77. Abstract
Kelley DB, Morrell JI, Pfaff DW Autoradiographic localization of hormone-concentrating cells in the brain of an amphibian, Xenopus laevis. I. Testosterone. J Comp Neurol. 1975 Nov 1; 164(1): 47-59. Abstract
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